Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Liver fibrosis is a critical pathological process in the progression of chronic liver diseases and is mainly driven by the activation of hepatic stellate cells， and it is characterized by excessive deposition of extracellular matrix. Programmed cell death is widely observed in liver fibrosis and plays diverse roles in different types of cells. It is not only a mechanism for maintaining cellular homeostasis through metabolism， but it can also regulate the development and progression of diseases. Ferroptosis has recently emerged as a research focus due to its close association with lipid metabolism. This article systematically reviews the related concepts of lipid metabolism， ferroptosis， and liver fibrosis， analyzes the bridging role and dual regulatory function of ferroptosis in lipid metabolism and liver fibrosis， and further highlights the clinical application value of targeting ferroptosis in hepatic stellate cells for the treatment of liver fibrosis， in order to provide new perspectives for the mechanistic studies on liver fibrosis and the optimization of related clinical intervention strategies.

ObjectiveTo investigate the effect and potential mechanism of Zhishi Daozhi Formula （枳实导滞方， ZDF） on inflammation in rats with sepsis-induced gastrointestinal dysfunction based on the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB （TLR4/MyD88/NF‑κB） signaling pathway and intestinal flora. MethodsSixty SD rats were randomly divided into sham‑operation group， model group， ulinastatin group， and low‑， medium‑ and high‑dose ZDF groups， with 10 rats in each group. Except for the sham‑operation group， the rat model of sepsis‑induced gastrointestinal dysfunction was established by cecal ligation and puncture （CLP）. Three days before modeling and 12 h after modeling， the low-， medium- and high-dose ZDF groups were intragastrically administered with ZDF solution at doses of 3.80， 7.60 and 15.20 g·kg⁻¹·d⁻¹， respectively. The ulinastatin group received intraperitoneal injection of ulinastatin at 100,000 U/kg， while the sham-operation and model groups were given normal saline at 1 ml/100 g by gavage. All interventions were performed once daily for 4 consecutive days. Tow hours after the last intervention， gastric emptying rate and small intestinal propulsion rate were detected. Gastrointestinal function indicators including D‑lactic acid （D‑LA） and intestinal fatty acid binding protein （i‑FABP）， as well as inflammatory indicators including procalcitonin （PCT） and C‑reactive protein （CRP） were measured by ELISA 24 h after modeling. The counts of Escherichia coli， Bifidobacterium and Lactobacillus in the intestine were compared. The histopathological morphological changes of the rat intestinal mucosa were observed by HE staining. The protein and mRNA expressions of IκB kinase （Ikk）， TLR4， MyD88 and NF‑κB in ileal tissues were detected by western blot and qRT‑PCR， respectively. ResultsCompared to the sham-operation group， the model group showed decreased gastric emptying rate and small intestinal propulsion rate， increased intestinal Escherichia coli count， elevated serum D‑LA， i‑FABP， PCT and CRP levels， increased protein and mRNA expressions of Ikk， TLR4， MyD88 and NF-κB in ileal tissue， decreased counts of Lactobacillus and Bifidobacterium （P＜0.05）， accompanied by obvious pathological injury of ileal mucosa. Compared to the model group， all medication groups exhibited significant improvements in the above mentioned indicators and alleviated intestinal mucosal injury （P＜0.05）. Compared to the ulinastatin group， except for D-LA in the medium-dose ZDF group， the differences in the above indicators between the low- and medium-dose ZDF groups were statistically significant （P＜0.05）， while the differences between the high-dose ZDF group and the ulinastatin group were not statistically significant （P＞0.05）. With increasing dosage， the gastric emptying rate， small intestinal propulsion rate， Lactobacillus and Bifidobacterium counts in the rats of all three ZDF groups increased， while the levels of serum D-LA， PCT， CRP， and i-FABP， the protein levels of Ikk， TLR4， MyD88， and NF-κB in intestinal tissue， and the Escherichia coli count decreased （P＜0.05）. ConclusionZDF can ameliorate intestinal mucosal injury， maintain intestinal flora balance and inhibit inflammatory response in rats with sepsis‑induced gastrointestinal dysfunction， with the high-dose group showing the best efficacy， which may be achieved by down‑regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective To study the seasonal distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in PM_2.5 in Lianyungang City, and analyze the sources of PAHs pollution, and to evaluate the health risks of PAHs in different seasons. Methods PM2.5 samples were collected regularly from January 2019 to December 2023, and 16 types of PAHs were determined by HPLC. Kruskal-Wallis H test was used to compare the concentrations of PM2.5 and PAHs in different years and seasons. The source of PAHs was analyzed by characteristic ratio and principal component analysis (PCA). Health risks were assessed using the BaP equivalent method and the incremental lifetime cancer risk (ILCR) model. Results The annual exceedance rates of PM_2.5 and BaP in Lianyungang showed a decreasing trend from 2019 to 2023. PM_2.5, total PAHs and PAHs monomers (except Ace, Flu and Acy) all showed significant seasonal differences, with the highest concentration in winter (P<0.001). The average proportion of 4-ring PAHs was the highest and the average proportion of 2-ring PAHs was the lowest. The proportion of 5-6 ring PAHs was relatively high in winter and spring. PM2.5and PAHs were negatively correlated with temperature, relative humidity and precipitation, and were positively correlated with atmospheric pressure. PM_2.5 was negatively correlated with wind speed, while some PAHs monomers were positively correlated with wind speed. The characteristic ratio and PCA results showed that the main sources of PAHs in Lianyungang City were mixed sources of road dust and vehicle emissions, oil pollution sources and biomass combustion sources. The results of ILCR showed that the highest risk was found in adults, with males slightly higher than females. In Lianyungang, the maximum value of ILCR in winter was more than 10-6 in people over 9 years old. Conclusion The main sources of PAHs in PM_2.5 in Lianyungang City are mixed sources of road dust and vehicle emissions, oil pollution sources, and biomass combustion sources. Under the current exposure level of PAHs in PM_2.5, residents have a certain potential carcinogenic risk.

Objective To analyze relevant literature on the essence of traditional Chinese medicine syndromes using bibliometric methods;To understand the current research status and hotspots in this field;To provide references for relevant research.Methods Research literature about the essence of TCM syndromes was retrieved from CNKI,VIP,Wanfang Data and CBM from 1st Jan.1979 to 30th June 2024.CiteSpace 6.2 software was used to conduct visualization analysis on authors,institutions,keywords,etc.Results A total of 695 articles were included,with an overall upward trend in publication volume followed by stabilization.The authors who published more articles included Luo Ren(13 articles),Zhao Xiaoshan(13 articles),Li Zegeng(12 articles),etc.The institutions with more publications included Shandong University of Traditional Chinese Medicine(35 articles),Beijing University of Chinese Medicine(33 articles),Chengdu University of Traditional Chinese Medicine(26 articles),etc.Institutions were clustered regionally,and cooperation was mostly between TCM universities and their affiliated hospitals,with less cross regional communication.High frequency keywords included kidney yang deficiency syndrome,metabolomics,animal models,TCM syndrome types,coronary heart disease,lung qi deficiency syndrome,spleen qi deficiency syndrome,liver depression and spleen deficiency syndrome,etc;Keyword clustering covered aspects such as biomolecules and metabolism,TCM syndromes,pathology,disease models,and animal research.Conclusion Research in the field of the essence of TCM syndromes is gradually receiving more attention.Exploring the essence of TCM syndromes at the molecular level through techniques such as genomics,transcriptomics,metabolomics and proteomics is a research hotspot and trend in this field.

AIM:This study aims to investigate whether vitamin E succinate(VES)induces autophagy in hu-man gastric cancer cells through the promotion of mitochondria-associated endoplasmic reticulum membranes(MAMs).METHODS:Human gastric cancer cell lines MKN28 and MKN45 were cultured in vitro.Cell viability was assessed us-ing the CCK8 assay,and two cell growth curves were plotted to determine the treatment concentration of VES.Control groups,VES dose groups(MKN28:5,10,20,and 40 mg/L;MKN45:10,20,40,and 80 mg/L),an autophagy-posi-tive control group(rapamycin,RAPA,100 nmol/L),and a MAMs-positive control group(oligomycin A,10 mg/L)were set up.Cells were harvested after 24 h of treatment for subsequent experiments.The formation of autophagosomes and MAMs was observed using transmission electron microscopy.The expression levels of autophagy-related proteins,includ-ing beclin-1,LC3-II/LC3-I,and p62,were detected by Western blot.MAMs labeled with split green fluorescent protein(GFP)were visualized by fluorescence microscopy.The expression of mitofusin 2(MFN2),a key molecule of MAMs,was also detected by Western blot.To inhibit MFN2 specifically,the cells were treated with mitochondrial fusion inhibitor 8(MFI8)and simultaneously transfected with an MFN2 plasmid to achieve MFN2 overexpression(OE-MFN2).The cells were divided into control group,MFI8(20 μmol/L)group,VES groups(20 mg/L for MKN28 cells and 40 mg/L for MKN45 cells),VES+MFI8 group,OE-MFN2+MFI8 group and OE-MFN2+VES+MFI8 group.The MAMs were visualized by fluorescence microscopy,and the expression changes of MFN2,beclin-1 and LC3-II/I were detected by Western blot.RESULTS:The results of the CCK8 assay showed that VES significantly inhibited the viability of both human gastric can-cer cell lines(P<0.05).After VES treatment,the formation of typical autophagosomes and MAMs was observed in both cell lines by transmission electron microscopy.Fluorescence microscopy showed a significant increase in GFP signals of MAMs.Western blot analysis showed that with increasing doses of VES,the expression levels of MFN2,beclin-1,and LC3-II/I were significantly up-regulated,while that of p62 was significantly down-regulated(P<0.05).Compared with VES group,the cells pretreated with MFI8 followed by VES exposure showed markedly reduced GFP signals of MAMs and much lower protein levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).Transfection with an MFN2 overexpression plasmid rescued MFN2 expression.Compared with VES+MFI8 group,the cells in OE-MFN2+VES+MFI8 group had much higher protein expression levels of MFN2,beclin-1 and LC3-II/LC3-I(P<0.05).CONCLUSION:The VES may partici-pates in the regulation of autophagy in human gastric cancer cells by promoting the formation of MAMs.

Objective:To investigate the early clinical outcomes of anterior cervical discectomy and fusion (ACDF) in the treatment of two-segment cervical spondylotic myelopathy (CSM) using a cervical soft endoscopic minimally invasive system.Methods:A retrospective follow-up study was conducted on the medical records of 23 patients with two-segment cervical myelopathy who underwent ACDF using a soft endoscopic cervical spine minimally invasive system at the Third Affiliated Hospital of Southern Medical University between October 2022 and December 2023. The cohort included 15 males and 8 females, aged 37-79 years (58.52±11.77 years). The affected cervical segments included: C 3, 4 and C 4, 5 in 2 cases; C 3, 4 and C 5, 6 in 3 cases; C 4, 5 and C 5, 6 in 10 cases; C 5, 6 and C 6, 7 in 7 cases; and C 4, 5 and C 6, 7 in 1 case. Clinical outcomes were evaluated based on the Japanese Orthopaedic Association (JOA) scores and visual analog scale (VAS) for neck and shoulder pain, assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Additional data recorded included incision length, intraoperative blood loss, operative time, postoperative complications, and the presence of prevertebral soft tissue edema. The improvement rate of JOA scores at the final follow-up was also calculated. Results:All patients successfully underwent surgery and completed follow-up, with follow-up durations ranging from 3 to 6 months (4.01±0.98 months). The mean operative time was 80.09±22.66 min (range: 53-127 min), and the mean incision length was 3.25±0.32 cm (range: 3-4 cm). Estimated blood loss ranged from 10 to 100 ml, with a mean of 34.78±24.1 ml. Postoperative drainage ranged from 0 to 80 ml (mean: 23.13±26.1 ml), and postoperative hospitalization durations ranged from 4 to 12 days (6.83±2.59 days). JOA scores improved significantly from a preoperative median of 9.00(8.00, 10.00) to 12.00(11.00, 14.00) at 1 week, 13.00(12.00, 14.00) at 1 month, and 15.00(15.00, 16.00) at 3 months postoperatively (χ 2=220.492, P<0.001). VAS scores for neck and shoulder pain also improved significantly from a preoperative median of 5.00(4.00, 6.00) to 3.00(2.00, 3.00) at 1 week, 2.00(2.00, 3.00) at 1 month, and 2.00(1.00, 2.00) at 3 months postoperatively (χ 2=170.869, P<0.001). No postoperative complications such as dysphagia, hoarseness, nerve injury, cerebrospinal fluid leakage, or intraspinal hematoma were observed. Imaging revealed no significant prevertebral soft tissue edema. At the final follow-up, the improvement rate of JOA scores resulted in 14 cases rated as excellent and 9 as good. Conclusions:ACDF using a cervical soft endoscopic minimally invasive system demonstrates satisfactory clinical outcomes for the treatment of two-segment CSM. This technique reduces the incidence of common complications associated with both open and traditional endoscopic surgeries.